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Better Drugs Needed to Battle New Forms of TB  
Wednesday, April 16, 2008 7:04 AM

As stronger and deadlier strains of tuberculosis emerge, current drugs used to treat the disease are becoming ineffective. But it...

As stronger and deadlier strains of tuberculosis emerge, current drugs used to treat the disease are becoming ineffective. But it may take many years to develop new medications that can tackle multi-drug and extremely drug resistant TB.

In 2006, the town of Tugela Ferry in South Africa's KwaZulu-Natal Province had already long been known as a place where HIV/AIDS had taken a tragic toll. But then things got worse. Something was killing patients more quickly than AIDS.

Fifty-three people had been stricken with what would become known as XDR-TB or Extremely Drug Resistant Tuberculosis. Fifty-two of them died very quickly. Those whose immune systems had been weakened by the AIDS virus were particularly vulnerable.

 It raised alarms among health officials and researchers. Dr. Paul Herrling, head of corporate research at Novartis International, says he had a gut reaction when he first heard the news about XDR-TB.

"Scared. I'm really scared," he says.

Herrling is chairman of the pharmaceutical company's Novartis Institute for Tropical Diseases, based in Singapore.

"What would be extremely frightening, and that's why I say scared, is that if ever we get a strain of resistant bacteria that might also be more fit or equally fit with the wild type, then it would take over the world really fast. And then you would have only resistant ones. And if then you don't have a new drug, you're lost," he says.

It nearly happened with malaria, he says, a few years ago.

"We practically had all over the world an increasing number of strains that were resistant to all existing drugs. And it's only now that we have the artemisin derivates - like Novartis has the biggest one - that we have found the tool again against resistant parasites in malaria," he says.

Health officials say the rise in MDR and XDR TB is due in part to the long treatment process for tuberculosis. It can take up to six months for drugs to clear the bacteria from the body. Unfortunately, some patients may not take their medication for the time required, thus allowing the TB bacteria to build up a resistance. It then becomes tougher if not impossible to treat.

Herrling says, "When a bacterium mutates to escape an antibiotic, it has to use some sort of alternative biochemical pathway in the body to avoid the one that is being shut off by the drug. That's how they do it."

The chairman of the Novartis Institute for Tropical Diseases says the facility is a not-for-profit research center. He says it's the company's contribution to the Access to Medicine project - an international effort to provide medications to all those in need.

However, despite the money and technology available for TB drug research, it's a slow process.

"If we look at the normal attrition rate and research and development times that you have for new drugs, it will be five to fifteen years until you have something available for the patients. And the problem is with TB, if XDR really becomes resistant to all existing drugs, one drug will not be enough. We'll have to do a combination of drugs, because if you let out only one drug against such a bacterium resistance will occur very fast," he says.

In the treatment of HIV/AIDS, for example, a combination of two or three drugs is usually given to deal with resistance. But that combination may have to be changed over the years as the AIDS virus gradually builds up resistance.

The Centers for Disease Control and Prevention says some TB control programs show that a cure is possible for XDR-TB, but it estimates only in 30 percent of affected people. That makes the need for newer, stronger drugs even more urgent. 

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